Approximately 20% of cardiac arrest "survivors" suffer permanent brain damage presenting a major social and medical-legal problem. Current clinical therapies for its prevention are hampered by lack of understanding of the pathological processes involved and proof of efficacy. A major obstacle has been the variability in animal models used. We recently developed a monkey model of total brain circulatory arrest (for 16 minutes) with 7-days postischemic life support, intensive care and monitoring of neurologic function. With this model, we demonstrated that thiopental (a short acting barbituate anesthetic) administered early postischemia in large doses (90mg/kg) significantly ameliorates permanent brain damage suggesting that much of the damage occurred after restoration of circulation and is amenable to therapy. The effectiveness of thiopental was significantly attenuated if administration was delayed or the administered dose reduced. The efficacy of thiopental is a result of improved brain oxygenation, brain glucose uptake and a "shift" of glucose into metabolic pathways other than to lactate (i.e., hexose monophosphate shunt). Studies on rats suggest that ischemic brain damage may be due to catecholamine-induced brain hypermetabolism and alterations in glucose utilization. On-going studies on thiopental are aimed at determining the optimal blood concentrations for effective amelioration of ischemic brain damage and the correlation between the thiopental anesthetic dose for monkeys compared to that for man. We recently evaluated the effect of bouts of arterial hypertension (mean arterial pressue of 150mmHg) postischemia on ischemic brain damage and found that hypertension worsened the brain damage and that precise arterial blood pressure control (plus or minus 10-20mmHg) upon restoration of circulation could have a profound effect on the ultimate degree of brain damage sustained.